Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers.

Authors

• Anup K Majumdar
• Laura Howard
• Michael R Goldberg
• Lisa Hickey
• Marvin Constanzer
• Paul L Rothenberg
• Tami M Crumley
• Deborah Panebianco
• Thomas E Bradstreet
• Arthur J Bergman
• Scott A Waldman
• Howard E Greenberg
• Kathleen Butler
• A Knops
• Inge De Lepeleire
• Nicole Michiels
• Kevin J Petty

Publication/Presentation Date

3-1-2006

Abstract

Aprepitant is the first NK1 receptor antagonist approved for use with corticosteroids and 5HT3 receptor antagonists to prevent chemotherapy-induced nausea and vomiting (CINV). The effective dose to prevent CINV is a 125-mg capsule on day 1 followed by an 80-mg capsule on days 2 and 3. Study 1 evaluated the bioavailability of the capsules and estimated the effect of food. The mean (95% confidence interval [CI]) bioavailabilities of 125-mg and 80-mg final market composition (FMC) capsules, as assessed by simultaneous administration of stable isotope-labeled intravenous (i.v.) aprepitant (2 mg) and FMC capsules, were 0.59 (0.53, 0.65) and 0.67 (0.62, 0.73), respectively. The geometric mean (90% CI) area under the plasma concentration time curve (AUC) ratios (fed/fasted) were 1.2 (1.10, 1.30) and 1.09 (1.00, 1.18) for the 125-mg and 80-mg capsule, respectively, demonstrating that aprepitant can be administered independently of food. Study 2 defined the pharmacokinetics of aprepitant administered following the 3-day regimen recommended to prevent CINV (125 mg/80 mg/80 mg). Consistent daily plasma exposures of aprepitant were obtained following this regimen, which was generally well tolerated.

Volume

46

Issue

3

First Page

291

Last Page

300

ISSN

0091-2700

Published In/Presented At

Majumdar, A. K., Howard, L., Goldberg, M. R., Hickey, L., Constanzer, M., Rothenberg, P. L., Crumley, T. M., Panebianco, D., Bradstreet, T. E., Bergman, A. J., Waldman, S. A., Greenberg, H. E., Butler, K., Knops, A., De Lepeleire, I., Michiels, N., & Petty, K. J. (2006). Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. Journal of clinical pharmacology, 46(3), 291–300. https://doi.org/10.1177/0091270005283467

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

16490805

Department(s)

Administration and Leadership

Document Type

Article